Exploration of the Tumor Transcriptomic and Immune Landscape Following Repeated Transurethral Resection in Non-Muscle-Invasive Bladder Cancer.

OBJECTIVE

To investigate the associations of repeated transurethral resection of bladder tumor (TURBT) and BCG treatment with molecular, immunological, and microbial landscapes of nonmuscle-invasive bladder cancer (NMIBC).

METHODS

Tumor and matched normal tissues from 24 NMIBC patients (primary TURBT, n = 12; repeated TURBT, n = 12) underwent RNA sequencing for transcriptomic and immune repertoire analyses. Urine samples were analyzed by 16S rRNA sequencing to characterize the urinary microbiome. Patients in the repeated TURBT group were further stratified by BCG treatment status (BCG-treated, n = 5; non-BCG, n = 7).

RESULTS

Repeated TURBT was associated with differences in transcriptomic reprogramming, immune remodeling, and urinary microbiome profiles compared with primary TURBT. Compared with primary tumors, repeated tumors exhibited a transcriptional shift from hypoxia- and metabolism-related pathways toward proliferative cell cycle programs and partial restoration of T and B cell receptor diversity. Microsatellite instability scores did not differ significantly between groups. BCG treatment primarily enhanced dendritic cell activation, reflecting innate immune stimulation without affecting adaptive repertoires. Urinary microbiome analysis revealed increased heterogeneity, with cyanobacteriota and Corynebacterium detected exclusively in patients who underwent repeated TURBT without BCG treatment.

CONCLUSION

In this exploratory cohort, repeated TURBT was associated with coordinated transcriptomic, immunologic, and microbial features in NMIBC. These preliminary findings suggest that surgical history may influence tumor-associated molecular and immune characteristics and warrant further investigation in larger, longitudinal studies.